Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria
The rise of antibiotic resistance is a critical public health concern, requiring an understanding of mechanisms that enable bacteria to tolerate antimicrobial agents. Bacteria use diverse strategies, including the amplification of drug-resistance genes. In this paper, we showed that multicopy plasmi...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2024
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| _version_ | 1797113178520289280 |
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| author | Hernandez-Beltran, JCR Rodríguez-Beltrán, J Aguilar-Luviano, OB Velez-Santiago, J Mondragón-Palomino, O Maclean, RC Fuentes-Hernández, A San Millán, A Peña-Miller, R |
| author_facet | Hernandez-Beltran, JCR Rodríguez-Beltrán, J Aguilar-Luviano, OB Velez-Santiago, J Mondragón-Palomino, O Maclean, RC Fuentes-Hernández, A San Millán, A Peña-Miller, R |
| author_sort | Hernandez-Beltran, JCR |
| collection | OXFORD |
| description | The rise of antibiotic resistance is a critical public health concern, requiring an understanding of mechanisms that enable bacteria to tolerate antimicrobial agents. Bacteria use diverse strategies, including the amplification of drug-resistance genes. In this paper, we showed that multicopy plasmids, often carrying antibiotic resistance genes in clinical bacteria, can rapidly amplify genes, leading to plasmid-mediated phenotypic noise and transient antibiotic resistance. By combining stochastic simulations of a computational model with high-throughput single-cell measurements of blaTEM-1 expression in Escherichia coli MG1655, we showed that plasmid copy number variability stably maintains populations composed of cells with both low and high plasmid copy numbers. This diversity in plasmid copy number enhances the probability of bacterial survival in the presence of antibiotics, while also rapidly reducing the burden of carrying multiple plasmids in drug-free environments. Our results further support the tenet that multicopy plasmids not only act as vehicles for the horizontal transfer of genetic information between cells but also as drivers of bacterial adaptation, enabling rapid modulation of gene copy numbers. Understanding the role of multicopy plasmids in antibiotic resistance is critical, and our study provides insights into how bacteria can transiently survive lethal concentrations of antibiotics. |
| first_indexed | 2024-03-07T08:16:14Z |
| format | Journal article |
| id | oxford-uuid:d6a233e4-e5b1-4913-a26b-9baaac588812 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-04-09T03:58:31Z |
| publishDate | 2024 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:d6a233e4-e5b1-4913-a26b-9baaac5888122024-04-03T15:11:57ZPlasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteriaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d6a233e4-e5b1-4913-a26b-9baaac588812EnglishSymplectic ElementsSpringer Nature2024Hernandez-Beltran, JCR Rodríguez-Beltrán, JAguilar-Luviano, OBVelez-Santiago, JMondragón-Palomino, OMaclean, RCFuentes-Hernández, ASan Millán, APeña-Miller, RThe rise of antibiotic resistance is a critical public health concern, requiring an understanding of mechanisms that enable bacteria to tolerate antimicrobial agents. Bacteria use diverse strategies, including the amplification of drug-resistance genes. In this paper, we showed that multicopy plasmids, often carrying antibiotic resistance genes in clinical bacteria, can rapidly amplify genes, leading to plasmid-mediated phenotypic noise and transient antibiotic resistance. By combining stochastic simulations of a computational model with high-throughput single-cell measurements of blaTEM-1 expression in Escherichia coli MG1655, we showed that plasmid copy number variability stably maintains populations composed of cells with both low and high plasmid copy numbers. This diversity in plasmid copy number enhances the probability of bacterial survival in the presence of antibiotics, while also rapidly reducing the burden of carrying multiple plasmids in drug-free environments. Our results further support the tenet that multicopy plasmids not only act as vehicles for the horizontal transfer of genetic information between cells but also as drivers of bacterial adaptation, enabling rapid modulation of gene copy numbers. Understanding the role of multicopy plasmids in antibiotic resistance is critical, and our study provides insights into how bacteria can transiently survive lethal concentrations of antibiotics. |
| spellingShingle | Hernandez-Beltran, JCR Rodríguez-Beltrán, J Aguilar-Luviano, OB Velez-Santiago, J Mondragón-Palomino, O Maclean, RC Fuentes-Hernández, A San Millán, A Peña-Miller, R Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria |
| title | Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria |
| title_full | Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria |
| title_fullStr | Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria |
| title_full_unstemmed | Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria |
| title_short | Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria |
| title_sort | plasmid mediated phenotypic noise leads to transient antibiotic resistance in bacteria |
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